WO2006017505A2 - Pharmaceutical formulations comprising pleconaril for the treatment of airway diseases - Google Patents
Pharmaceutical formulations comprising pleconaril for the treatment of airway diseases Download PDFInfo
- Publication number
- WO2006017505A2 WO2006017505A2 PCT/US2005/027428 US2005027428W WO2006017505A2 WO 2006017505 A2 WO2006017505 A2 WO 2006017505A2 US 2005027428 W US2005027428 W US 2005027428W WO 2006017505 A2 WO2006017505 A2 WO 2006017505A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- medicament according
- dispersion
- propellant
- pharmaceutically acceptable
- finely divided
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
Definitions
- the present invention is directed to formulations containing Pleconaril either alone or in combination with one or more other pharmaceutically active ingredients in novel dosage forms and methods of using the same.
- Pleconaril is known as 1 ,2,4-oxadiazole3-[3,5-Dimethyl-4-[3-(3-methyl-5- isoxazolyl)propoxy]phenyl]-5-(trifluoremethyl). It has other names such as PICOVIR®, VP 63843 and Win 63843. It has been shown to be active against rhinoviruses. Due to the efficacy of Pleconaril as an anti-viral agent for the treatment of the common cold, it would be beneficial to administer it along with other medications and/or in certain dosage forms that relieve symptoms associated with the common cold, viral induced respiratory diseases and/or other disease states.
- the corticosteroid is Mometasone Furoate monohydrate.
- Pleconaril or a pharmaceutically acceptable salt thereof and (B) an antihistamine, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- the antihistamine is Desloratadine or loratadine.
- a medicament containing, separately or together, (A)
- Pleconaril or a pharmaceutically acceptable salt thereof and (B) an expectorant, for _ _
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) an NSAID, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) a decongestant for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) an anticholinergic, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) an anticholinergic, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- A) Pleconaril or a pharmaceutically acceptable salt thereof for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- A) Pleconaril or a pharmaceutically acceptable salt thereof for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) an antibiotic, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) an H 3 antagonist, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) a Leukotriene 4 antagonist, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) an P2Y 2 agonist, for simultaneous, sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- a medicament containing, separately or together, (A) Pleconaril or a pharmaceutically acceptable salt thereof and (B) a syk kinase antagonist, for sequential or separate administration in the treatment of an upper or lower respiratory, viral, inflammatory or obstructive airways disease.
- medicaments of the present invention will have advantages over medicaments containing only pleconaril as the active agent.
- the medicaments of the present invention containing Pleconaril and one or more active agents described above when formulated together for administration using a nebulizer have advantages including but not limited to oral administration, ease of pediatric therapy and/or high dose loading availability
- the medicaments of the present invention containing Pleconaril and one or more of the other active agents described above can be formulated as a metered dose inhaler product, that may be administered either orally or nasally simply by switching the actuator that is designed ofr nasal delivery with an actuator designed for oral delivery.
- Pleconaril is known as 1 ,2,4-oxadiazole3-[3,5-Dimethyl-4-[3-(3-methyl-5- isoxazolyl)propoxy]phenyl]-5-(trifluoromethyl). It has other names such as PICOVIR®, VP 63843 and Win 63843.
- Pleconaril is a picornavirus replication inhibitor useful in the treatment of, amongst other things, viral induced infections of the upper and lower airways, viral meningitis, and life-threatening diseases such as chronic meningoencephalitis, neonatal enteroviral disease, polio and myocarditis. According to the Merck Index, it may be prepared in accordance with U.S. Patent No.
- Pleconaril may be combined with a corticosteroid.
- Corticosteroids for use in the present invention include mometasone furoate, dexamethasone, butoxicort, rofleponide, budesonide, deflazacort, ciclesonide, fluticasone, beclomethasone, loteprednol or triamcinolone.
- a particularly preferred corticosteroid is Mometasone Furoate. Mometasone
- Furoate is a corticosteroid approved for topical dermatologic use to treat inflammatory and/or pruritic manifestations of corticosteroid-responsive dermatoses.
- the compound may be prepared in accordance with the procedures disclosed in U.S. Patent Nos. 4,472,393, 4,731 ,447, 4,873,335, 5,837,699 and 6,127,353, all of which are hereby incorporated by reference in their entirety.
- Mometasone Furoate is a topically active steroid which is not readily bioavailable. It is commercially available as a spray for intra-nasal administration under the name of Nasonex®. Mometasone's use for the treatment of airway passages and lung diseases is disclosed in U.S. Patent Nos.
- the substantially non-systematically bioavailable amount of Mometasone Furoate which may be administered as an aqueous suspension or dry powder is in the range of about 10 to 5000 micrograms ("mcg")/day, 10 to 4000 meg/day, 10 to 2000 meg/day, 25-1000 meg/day, 25 to 400 meg/day, 25-200 meg/day, 25-100 meg/day or 25-50 meg/day in single or divided doses.
- the corticosteroid when the corticosteroid is fluticasone, it may be administered at the dose of 2 sprays of 50 ⁇ g of fluticasone propionate each in each nostril once daily. Alternatively, it may be administered at a dose of fluticasone is 1 spray of 50 ⁇ g of fluticasone propionate each in each nostril once daily.
- the corticosteroid when the corticosteroid is triamcinolone, it may be administered at a dose of triamcinolone is 220 ⁇ g per day as two sprays in each nostril once daily. Alternatively, it may be administered at a dose of 110 ⁇ g per day as one spray in each nostril once daily.
- the administered dose of budesonide may be 64 ⁇ g per day administered as one spray per nostril of 32 ⁇ g once daily.
- Pleconaril can be combined with an histamine Hi receptor antagonist that is selected from the group consisting of Astemizole, Azatadine, Azelastine, Acrivastine, Bromphemiramine, Chlorpheniramine, Clemastine, Cyclizine, Carebastine, Cyproheptadine, Carbinoxamine, Desloratadine, Doxylamine, Diphenhydramine, Cetirizine,
- Pleconaril and antihistamine(s) may be administered both orally and topically. Topical and oral administration may be carried out as set forth herein.
- Desloratadine is a non-sedating antihistamine, whose technical name is 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5H- benzo[5,6]cyclohepta[1 ,2]pyridine.
- This compound is described in Quercia, et al., Hosp. Formul., 28: 137-53 (1993), in U.S. Patent 4,659,716, and in WO 96/20708.
- the use of Desloratadine for the treatment of congestion is disclosed in U.S. Patent No. 6,432,972.
- DCL is an antagonist of the Hi histamine receptor protein.
- the Hi receptors are those that mediate the response antagonized by conventional antihistamines.
- H 1 receptors are present, for example, in the ileum, the skin, and the bronchial smooth muscle of man and other mammals.
- the amount of DCL which can be employed in a unit (i.e. single) dosage form of the present compositions can range from about 2.5 to about 45 mg, also from about 2.5 to about 20 mg, also from about 5 to about 10 mg.
- Preferred dosage amounts include 2.5 mg, 5.0 mg, 10.0 mg and 20.0 mg.
- Loratadine is a non-sedating antihistamine whose technical name is 11 -(4-piperidylidene)-5H-benzo- [5, 6]-cyclohepta-[1 , 2-b]-pyridine. The compound is described in U.S. Patent No. 4,282,233. Loratadine is a potent tricyclic and antihistaminic drug of slow release, with a selective antagonist of peripheric Hi receptors activity. _ _
- Fexofenadine Another antihistamine for use with Pleconaril is Fexofenadine.
- Fexofenadine reportedly is a non-sedating antihistamine, whose technical name is 4-[1-hydroxy-4- (4-hydroxy-diphenylmethyl)-1-piperidinyl)butyl]- ⁇ , ⁇ -dimethyl-benzene acetic acid.
- the pharmaceutically acceptable salt is the hydrochloride, also known as fexofenadine hydrochloride.
- the amount of fexofenadine which can be employed in a unit dosage form of the present composition can range from about 40 to 200 mg, also from about 60 to about 180 milligrams, also about 120 milligrams.
- Cetirizine hydrochloride reportedly is an Hi receptor antagonist.
- the chemical name is ( ⁇ ) - [2- [4- [ (4-chlorophenyl)phenylmethyl] -1- piperazinyl] ethoxyjacetic acid, dihydrochloride.
- Cetirizine hydrochloride is a racemic compound with an empirical formula of C 21 H 25 CIN 2 O 3 -2HCI.
- Cetirizine hydrochloride is a white, crystalline powder and is water soluble.
- Cetirizine hydrochloride is available from Pfizer Inc., New York, NY, under the trade name ZYRTEC®.
- the amount of Cetirizine which can be employed in a unit dosage form of the present composition can range from about 0 to 40 mg, also from about 5 to about 10 milligrams.
- the levo isomer of Cetirizine may also be combined with Pleconaril in the formulations of the present invention.
- Another form of Cetirizine for use in the present invention is Cetirizine dinitrate.
- Ambroxol is a bromhexine metabolite, chemically identified as trans-4(2-amino-3,5-dibromobenzil, amine) ciclohexane hydrochloride, which has been widely used during more than two decades as an expectorant agent or stimulating pulmonary surfactant factor.
- the compound is described in U.S. Patent No. 3,536,712.
- Guaiafenesin is an expectorant, whose technical name is 3-(2-methoxyphenoxy)- 1 , 2-propanediol.
- the compound is described in U.S. Patent No. 4,390,732.
- Terpin hydrate is an expectorant, whose technical name is 4-hydroxy- ⁇ , ⁇ , 4-trimethylcyclohexane-methanol.
- Potassium guaicolsulfonate is an expectorant, whose technical name is 3-Hydroxy-4- methoxybenzenesulfonic acid mix with mono-potassium 4-hydroxy-3- methoxybenzenesulfonate.
- nasal decongestants useful in the present invention include the sympathomimetic amine nasal decongestants.
- Those currently approved for topical use in the United States include, without limitation, levmetamfetamine (also known as 1-desoxyephedrine), ephedrine, ephedrine hydrochloride, ephedrine sulfate, naphazoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, propylhexedrine and xylometazoline hydrochloride.
- levmetamfetamine also known as 1-desoxyephedrine
- ephedrine ephedrine hydrochloride
- ephedrine sulfate ephedrine sulfate
- naphazoline hydrochloride oxymetazoline hydrochloride
- phenylephrine hydrochloride phenylephrine hydrochloride
- Oral decongestants for use in the present invention include phenylpropanolamine, phenylephrine and pseudoephedrine.
- Pseudoephedrine as well as pharmaceutically acceptable acid additional salts e.g., those of HCI or H 2 SO 4( is a sympathomimetic drug recognized by those skilled in the art as a safe therapeutic agent effective for treating nasal congestion and is commonly administered orally and concomitantly with an antihistamine for treatment of nasal congestion associated with allergic rhinitis.
- the use of pseudoephedrine as a nasal decongestant in the present invention is preferred in amounts of about 120 mg pseudoephedrine sulfate dosed one to 4 times daily. However, lesser amounts of pseudoephedrine sulfate may be used in combination with Pleconaril.
- Specific drugs in combination with Pleconaril that may be incorporated when the composition is intended to relieve oropharyngeal discomfort, such as sore throat, cold or canker sores, painful gums and other conditions are topical anesthetics such as phenol, hexylresorcinol, salicyl alcohol, benzyl alcohol, dyclonine, dibucaine, benzocaine, buticaine, cetylpyridinium chloride, diperidon, clove oil, menthol, camphor, eugenol and others.
- topical anesthetics such as phenol, hexylresorcinol, salicyl alcohol, benzyl alcohol, dyclonine, dibucaine, benzocaine, buticaine, cetylpyridinium chloride, diperidon, clove oil, menthol, camphor, eugenol and others.
- drugs that may be incorporated for application to the skin for relieving discomfort include lidocaine, benzoca
- histamine H 3 receptor antagonists are also for use in combination with Pleconaril.
- histamine H 3 receptor include, without limitation: Thioperamide, Impromidine, Burimamide, Clobenpropit, Impentamine, Mifetidine, S- sopromidine, R-sopromidine, 3-(imidazol-4-yl)-propylguanidine (SKF-91486), 3->(4- chlorophenyl)methyl-5->2-(1 H-imidazol-4yl)ethyl 1 ,2,3-oxadiazole (GR-175737), 4-(1 - cyclohexylpentanoyl-4-piperidyl) 1 H-imidazole (GT-2016), 2- ⁇ >2->4(5)- imidazolylethylthio ⁇ -5-nitropyridine (UCL-1199) Clozapine, SCH497079 and _ _
- SCH539858 Particularly preferred compounds are disclosed and claimed in U.S. Patent No. 6,720,328 and United States Patent Application Publication No.20040097483A1 , both assigned to Schering Corp., and both of which are hereby incorporated by reference.
- Other preferred compositions may further include both Hi and H 3 receptors antagonists as is disclosed in U.S. Patent 5,869,479, also assigned to Schering Corp., which is hereby incorporated by reference.
- Other compounds can readily be evaluated to determine activity at H 3 receptors by known methods, including the guinea pig brain membrane assay and the guinea pig neuronal ileum contraction assay, both of which are described in U.S. Pat. No. 5,352,707.
- Another useful assay utilizes rat brain membranes and is described by West et al.,
- Anti-Cholinergic agents include Tiotropium, Oxitropium, Ipratropium, Methantheline, Propantheline, Dicyclomine, Scopolamine, Methscopolamine, Telenzepine, Benztropine, QNX-hemioxalate, Hexahydro-sila- difenidol hydrochloride and Pirenzepine. These compositions may be administered either orally or nasally as set forth below in amounts that are known to one of skill in the art.
- Antibiotics for use in combination with Pleconaril in the present invention include antibiotics such as Tetracycline, Chlortetracycline, Bacitracin, Neomycin, Polymyxin, Gramicidin, Oxytetracycline, Chloramphenicol, Florfenicol, Gentamycin, Erythromycin, Clarithromycin, Azithromycin, Tulathromycin, or other suitable macrolide, Cefuroxime, Ceftibuten, Ceftiofur, Cefadroxil, or other suitable cephalosporin, Amoxicillin, Peniccilins, Amoxicillin with clavulanic acid or an other suitable beta-lactamase inhibitor, antibacterials such as Sulfonamides, Sulfacetamide, Sulfamethizole, Sulfisoxazole; Nitrofurazone, and Sodium propionate.
- antibiotics such as Tetracycline, Chlortetracycline, Bacitracin, Neomycin, Polymyxin, Gramici
- compositions may be administered either orally or nasally as set forth below in amounts that are known to one of skill in the art.
- Other agents for use within the scope of the present invention include P2Y 2 receptor agonists in combination with Pleconaril.
- Diquafosol tetrasodium is a P2Y 2 receptor agonist that activates receptors on the ocular surface and inner lining of the _
- Mucin is made in specialized cells and acts to lubricate surfaces. Lipids in the eye are oily substances that form the outer-most layer of the tear film and are responsible for the prevention of excess tear fluid evaporation. In preclinical testing, diquafosol reportedly increased the secretions of natural tear components. Diquafosol is available from Inspire.
- P2Y 2 receptor agonists are a new class of compounds that are being developed for the treatment of a variety of conditions in which MCC is impaired, including chronic bronchitis and CF. Other mucolytic agents may include N-Acetylcysteine and endogenous ligand compound UTP. These compositions may be administered either orally or nasally as set forth below in amounts that are known to one of skill in the art.
- NSAID's Non-Steroidal Anti- Inflammatory agents.
- Suitable NSAID's include Acetylsalicylic acid, Acetaminophen, Indomethacin, Diclofenac, Piroxicam, Tenoxicam, Ibuprofen, Naproxen, Ketoprofen, Nabumetone, Ketorolac, Azapropazone, Mefenamic acid, Tolfenamic acid, Sulindac, Diflunisal, Tiaprofenic acid, Podophyllotoxin derivatives, Acemetacin, Aceclofenac, Droxicam, Oxaprozin, Floctafenine, Phenylbutazone, Proglumetacin, Flurbiprofen, Tolmetin and Fenbufen.
- These compositions may be administered either orally or nasally as set forth below in amounts that are known to one of skill in the art.
- Leukotriene 4 Antagonists include Zileuton, Docebenone, Piripost, ICI-D2318, MK-591 , MK-886, sodium 1-(((R)-(3-(2-(6,7-difluoro-2- quinolinyl)ethynyl)phenyl)-3-(2-(2-hydroxy-2 - propyOphenyOthioJmethyOcyclopropane-acetate; 1-(((1 (R)-(3-(2-(2,3- dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)phenyl )-3-(2-(1 -hydroxy-1 - methylethyl)phenyl)propyl)thio)-methyl)cyclopropaneacetic acid, Pranlukast, Zafirlukast, and Monteluk
- Montelukast is a Leukotriene D 4 antagonist capable of antagonizing the receptors for the cysteinyl leukotrienes.
- the technical name of Montelukast is [R- (E)]-1 -[[[1 -[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1 -hydroxy-1 - methylethyl)phenyl]propyl]thio]methyl]-cyclopropaneacetic acid. This compound is described in EP 480,717.
- a preferred pharmaceutically acceptable salt of Montelukast is the monosodium salt, also known as Montelukast sodium.
- the amount of Montelukast which can be employed in a unit dosage form of the present invention can range from about one to 100 milligrams, also from about 5 to about 20 milligrams, preferably about 10 milligrams.
- the compound 1-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl)ethenyl)phenyl)-3-(2-(2- hydroxy-2-propyl)phenyl)thio)methylcyclopropaneacetic acid is a leukotriene antagonist described in WO 97/28797 and U.S. Patent No. 5,270,324.
- a pharmaceutically acceptable salt of this compound is the sodium salt, also known as sodium 1-(((R)-(3- (2-(6,7-difluoro-2-quinolinyl)ethenyl)phenyl)-3-(2-(2-hydroxy-2-propyl) phenyl)thio)- methylcyclopropaneacetate.
- the compound 1-(((1(R)-3(3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)- ethenyl)phenyl)-3-(2-(1 -hydroxy-1 -methylethyl)phenyl)propyl)- thio)methyl)cyclopropaneacetic acid is a leukotriene antagonist described in WO 97/28797 and U.S. Patent No. 5,472,964.
- a pharmaceutically acceptable salt of this compound is the sodium salt, also known as sodium 1-(((1(R)-3(3-(2-(2,3- dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)phenyl)-3-(2-(1 -hydroxy-1 - methylethyl)phenyl)propyl)-thio)methyl)cyclopropaneacetate.
- Pranlukast is a leukotriene antagonist described in WO 97/28797 and EP
- the technical name for this compound is N-[4-oxo-2-(1H-tetrazol-5-yl)-4H- 1-benzopyran-8-yl]-p-(4-phenylbutoxy)benzamide.
- the amount of Pranlukast which can be employed in a unit dosage form can range from about 100 to about 700 mg, preferably from about 112 to about 675 mg; also from about 225 mg to about 450 mg; also from about 225 to about 300 mg.
- Zafirlukast is a leukotriene antagonist described in WO 97/28797 and EP 199,543.
- the technical name for this compound is cyclopentyl-3-[2-methoxy-4-[(o- tolylsulfonyl)carbamoyl]benzyl]-1-methylindole-5-carbamate.
- the compound [2-[[2-(4-terf-butyl-2-thiazolyl)-5- benzofuranyl]oxymethyl]phenyl]acetic acid is a leukotriene antagonist and/or inhibitor _ _
- the solution contains substantially unchelated zinc ions in a concentration of from about 0.004 to about 0.12% (w/vol), to the nostrils and respiratory tract of a patient in need thereof.
- the solution can be selected from the group consisting of aqueous and saline solutions;
- the substantially unchelated ionic zinc compound can comprise a mineral acid salt of zinc; can comprise a salt selected from the group consisting of zinc sulfate and zinc chloride, such as zinc acetate, are generally preferable.
- These compositions may be administered either orally or nasally as set forth below in amounts that are known to one of skill in the art.
- Pleconaril in the present invention are compounds known for the treatment of the common cold such as echinacea, Vitamin C, Vitamin E, anti- oxidants and the like.
- Pleconaril in the present invention are a class of molecules which work via a novel mechanism, blocking syk kinase, such as R112, available from Rigel Pharmaceuticals, Inc.
- R112 blocking syk kinase
- a recent study reportedly showed a greater than 20% relative improvement for R112 over placebo (an absolute difference of 9% over placebo) and up to 38% improvement for R112 from baseline measurements (prior to drug initiation).
- symptoms most closely associated with chronic nasal congestion e.g. stuffy nose
- 5-lipoxygenase inhibitors are also for use with Pleconaril in the present invention.
- the term “5-lipoxygenase inhibitor” or “5-LO inhibitor” includes any agent, or compound that inhibits, restrains, retards or otherwise interacts with the enzymatic action of 5-lipoxygenase, such as, but not limited to, zileuton, docebenone, piripost, and the like.
- the term “5-lipoxygenase activating protein antagonist” or “FLAP antagonist” includes any agent or compound that inhibits, retrains, retards or otherwise interacts with the action or activity of 5-lipoxygenase activating protein, such as, but not limited to MK-591 and MK-886.
- the formulations of the present invention may contain Pleconaril either alone or in combination with one or more pharmacologically active agents as set forth herein.
- the formulation may contain Pleconaril in combination with Desloratadine and/or Pseudoephedrine for the treatment of a respiratory, viral, inflammatory or obstructive airways disease.
- the devices found useful for providing measured substantially non- systematically bioavailable amounts of aerosolized pharmaceutical compositions thereof for delivery to the oral airway passages and lungs by oral inhalation or intranasally by inhalation include pressurized metered-dose inhalers ("MDI") which deliver aerosolized particles suspended in chlorofluorocarbon propellants such as CFC-11 , CFC-12, or the non-chlorofluorocarbons or alternate propellants such as the fluorocarbons, HFC-134A or HFC-227 with or without surfactants.
- MDI pressurized metered-dose inhalers
- the formulations of the present invention may be also administered in specific, measured amounts in the form of an aqueous suspension by use of a pump spray bottle such as the bottles used to deliver NASONEX® Nasal Spray as well as the spray bottle disclosed in the Schering Corporation Industrial Design Deposit DM/026304, registered by the Hague Union on Jun. 1 , 1993 (each are available from Schering Corporation).
- a pump spray bottle such as the bottles used to deliver NASONEX® Nasal Spray as well as the spray bottle disclosed in the Schering Corporation Industrial Design Deposit DM/026304, registered by the Hague Union on Jun. 1 , 1993 (each are available from Schering Corporation).
- the delivery device may comprise 2 interchangeable actuators, respectively, for both oral and nasal delivery to treat both the oral and nasal sites of viral activity.
- a typical actuator for nasal delivery may be circular with an orifice diameter of about one millimeter.
- An actuator for use in oral delivery can be enclosed within a mouthpiece and the actuator typically has an orifice diameter of about 0.5 millimeters.
- the formulations of the present invention may also be administered via a Dry Powder Inhaler.
- dry Powder Inhalers include, without limitation, Schering's Twisthaler, Diskhaler (Allen & Hanburys), Accuhaler (Allen & Hanburys), Diskus (Glaxo), Spiros (Dura), Easyhaler (Orion), Cyclohaler (Pharmachemie), Cyclovent (Pharmachemie), -
- Rotahal ⁇ r (Glaxo), Spinhaler (Fisons), FlowCaps(Hovione), Turbospin (PH&T), Turbohaler (Astra), EZ Breath (Norton Healthcare/IVAX), MIAT-HALER (Miat), Pulvinal (Chiesi), Ultrahaler (Fisons/Rhone Poulenc Rorer), MAG-Haler (GGU), Prohaler (Valois), Taifun (Leiras), JAGO DPI (JAGO), and M L Laboratories' DPI (M L Laboratories).
- the formulations of the present invention may also be administered via a nebulizer device.
- Typical commercial nebulizer devices produce dispersions of droplets in gas streams by one of two methods. Jet nebulizers use a compressed air supply to draw up a fluid by venturi action and introduce it into a flowing gas stream, after which the fluid is caused to impact one or more stationary baffles to remove excessively large droplets.
- Jet nebulizers use an electrically driven transducer to subject a fluid to high-frequency oscillations, producing a cloud of droplets which can be entrained in a moving gas stream; these devices are less preferred for delivering suspensions.
- Suspension formulations suitable for nebulization must, of course, contain solid particles of a respirable size (e.g., preferably averaging less than about 5 .mu.m in the largest dimension and more preferably averaging less than about 2 .mu.m) and must maintain their suspended particle size distribution during storage.
- the particle-containing droplets formed during nebulization of the formulations must have appropriate sizes for deposition in the desired area of the respiratory system.
- the product may contain 2 interchangeable actuators. For instance, it could contain one actuator for nasal administration and one actuator for oral administration. _
- a pharmaceutically acceptable carrier which includes diluents, excipients or carrier materials
- the carrier is suitably selected with respect to the intended form of administration, i.e. oral tablets, capsules (either solid-filled, semi-solid filled or liquid filled), powders for constitution, oral gels, elixirs, syrups, suspensions, and the like, and consistent with conventional pharmaceutical practices.
- the active drug component may be combined with any oral non-toxic pharmaceutically acceptable inert carrier, such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, ethyl alcohol (liquid forms) and the like.
- suitable binders, lubricants, disintegrating agents, disinfectants and coloring agents may also be incorporated in the mixture.
- suitable binders include starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes.
- compositions of the present invention may be formulated in sustained release form to provide the rate controlled release of any one or more of the components or active ingredients to optimize the therapeutic effects.
- Suitable dosage forms for sustained release include layered tablets containing layers of varying disintegration rates or controlled release polymeric matrices impregnated with the active components and shaped in tablet form or capsules containing such impregnated or encapsulated porous polymeric matrices.
- Dosage form - refers to composition containing the antihistamine and the carrier formulated into a delivery system, i.e., tablet, capsule, oral gel, powder for constitution or suspension in association with inactive ingredients.
- Capsule - refers to a special container or enclosure made of methyl cellulose, polyvinyl alcohols, or denatured gelatins or starch for holding or containing compositions comprising the antihistamine and the carrier.
- Hard shell capsules are typically made of blends of relatively high gel strength bone and pork skin gelatins. The capsule itself may contain small amounts of dyes, opaquing agents, plasticizers and preservatives.
- Tablet- refers to a compressed or molded solid dosage form containing the ingredients (the antihistamine and the carrier) with suitable diluents.
- the tablet can be prepared by compression of mixtures or granulations obtained by wet granulation, dry granulation or by compaction.
- Oral gels refers to the antihistamine and the carrier dispersed or solubilized in a hydrophilic semi-solid matrix.
- Powders for constitution refers to powder blends containing the antihistamine and the carrier and suitable diluents which can be suspended in water or juices.
- Diluent - refers to substances that usually make up the major portion of the composition or dosage form. Suitable diluents include sugars such as lactose, sucrose, mannitol and sorbitol; starches derived from wheat, corn rice and potato; and celluloses such as microcrystalline cellulose.
- the amount of diluent in the composition can range from about 10 to about 90% by weight of the total composition, preferably from about 25 to about 75%, more preferably from about 30 to about 60% by weight, even more preferably from about 12 to about 60%.
- Disintegrants refers to materials added to the composition to help it break apart (disintegrate) and release the medicaments.
- Suitable disintegrants include starches; "cold water soluble" modified starches such as sodium carboxymethyl starch; natural and synthetic gums such as locust bean, karaya, guar, tragacanth and agar; cellulose derivatives such as methylcellulose and sodium carboxymethylcellulose; microcrystalline celluloses and cross-linked microcrystalline celluloses such as sodium croscarmellose; alginates such as alginic acid and sodium alginate; clays such as bentonites; and effervescent mixtures.
- the amount of disintegrant in the composition can range from about 2 to about 15% by weight of the composition, more preferably from about 4 to about 10% by weight.
- Binders - refers to substances that bind or "glue” powders together and make them cohesive by forming granules, thus serving as the "adhesive" in the formulation. Binders add cohesive strength already available in the diluent or bulking agent. Suitable binders include sugars such as sucrose; starches derived from wheat, corn rice and potato; natural gums such as acacia, gelatin and tragacanth; derivatives of seaweed such as alginic acid, sodium alginate and ammonium calcium alginate; cellulosic materials such as methylcellulose and sodium carboxymethylcellulose and hydroxypropylmethylcellulose; polyvinylpyrrolidinone; and inorganics such as magnesium aluminum silicate.
- the amount of binder in the composition can range from about 2 to about 20% by weight of the composition, more preferably from about 3 to about 10% by weight, even more preferably from about 3 to about 6% by weight.
- Lubricant - refers to a substance added to the dosage form to enable the tablet, granules, etc. after it has been compressed, to release from the mold or die by reducing friction or wear.
- Suitable lubricants include metallic stearates such as magnesium stearate, calcium stearate or potassium stearate; stearic acid; high melting point waxes; and water soluble lubricants such as sodium chloride, sodium benzoate, sodium acetate, sodium oleate, polyethylene glycols and d'l-leucine. Lubricants are usually added at the very last step before compression, since they must be present on the surfaces of the granules and in between them and the parts of the tablet press.
- the amount of lubricant in the composition can range from about 0.2 to about 5% by weight of the composition, preferably from about 0.5 to about 2%, more preferably from about 0.3 to about 1.5% by weight.
- Glidants - materials that prevent caking and improve the flow characteristics of granulations, so that flow is smooth and uniform.
- Suitable glidants include silicon dioxide and talc.
- the amount of glidant in the composition can range from about 0.1% to about 5% by weight of the total composition, preferably from about 0.5 to about 2% by weight.
- Coloring agents - excipients that provide coloration to the composition or the dosage form. Such excipients can include food grade dyes and food grade dyes adsorbed onto a suitable adsorbent such as clay or aluminum oxide.
- the amount of the coloring agent can vary from about 0.1 to about 5% by weight of the composition, preferably from about 0.1 to about 1%.
- Bioavailability - refers to the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed into the systemic circulation from an . .
- administered dosage form as compared to a standard or control, as well as to topical bioavailability.
- the compositions of the present invention may take various forms.
- they may be an aqueous gel or liquid, or an ointment.
- the composition is a water-in-oil emulsion with the active ingredients in the aqueous droplets suspended in a lotion orflowable ointment base comprising, e.g., petrolatum, mineral oil, and the like. Additional emollient ingredients such as isopropyl myristate may also be added.
- a lotion or ointment covers the conjunctiva and cornea with a thin film that both carries active ingredients and provides for prolonged drainage through the naso-lacrimal ducts.
- the film also provides a barrier to evaporative loss of water from the corneal stroma.
- pharmaceutically acceptable salt refers to a salt prepared from pharmaceutically acceptable non-toxic acids or bases including inorganic acids or bases or organic acids or bases. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, sulfuric, and phosphoric.
- Appropriate organic acids may be selected, for example, from aliphatic, aromatic, carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, glucuronic, maleic, furoic, glutamic, benzoic, anthranilic, salicylic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, pantothenic, benzenesulfonic, stearic, sulfanilic, algenic, and galacturonic.
- inorganic bases include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc.
- Appropriate organic bases may be selected, for example, from N,N ⁇ dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumaine (N-methylgulcaine), lysine and procaine.
- Pleconaril and active agent combination and the optional ingredient or ingredients may be administered in combination or separately in the method of treating the disease. For example, they may be administered concurrently or _ _
- terapéuticaally effective amount means that amount of the Pleconaril and one or more pharmaceutically active agents which provides a therapeutical benefit in the treatment or management of the disease or disease states.
- compositions of the present invention may be used for the treatment of a number of viral based disorders including the treatment and/or prevention of the common cold.
- the compositions of the present invention may be used for the prevention of exacerbation of disorders of the upper and lower airways such as allergic rhinitis, congestion associated therewith nasal blockage associated therewith, asthma, chronic obstructive pulmonary disorder, allergic asthma, emphysema, to prevent the need for rescue the use of rescue medications for disorders of the lower airways, sinusitis, fungal induced sinusitis, bacterial based sinusitis, polyposis and the like.
- the formulations of the present invention may also be used for viral based post exposure treatment.
- compositions may also be used prophylactically when a household member, typically a child, is stricken with a cold. Alternatively, it may be used in settings where there is a high incidence of viral or bacterial based pathogens such as in a hospital, nursing home, pharmacy and the like.
- the compositions of the present invention may also be used prophylactically to prevent exacerbations of symptoms associated with diseases of the upper airways in individuals with such diseases.
- the severity of the disease state in a patient can be quantified by objective pulmonary function tests, including a measurement of the patient's forced expiratory volume in 1 second (FEVi).
- FEVi forced expiratory volume in 1 second
- the airway obstruction is considered to be mild.
- FEV 1 value about 50 to 64 percent of predicted, the airway obstruction is classified as moderate; if the value is less than 50 percent of predicted, the airway obstruction is considered to be severe; and if the value is less than 30 percent the airway obstruction is considered to be very severe.
- This test utilizes relatively simple and inexpensive equipment, and therefore is widely used for disease state diagnosis, and to monitor the progression lung and airway disorders during treatment.
- Efficacy endpoints studies may include were Total Symptom Score, Total Nasal Symptom Score, Total Non-nasal Symptom Score, and Health Quality of Life (HQOL) analysis in efficacy trials.
- the compositions of the present invention may be tested for reducing the total symptom scores (the sum of individual scores for rhinorrhea, sneezing, congestion/stuffiness, nasal itching, itchy/burning eyes, tearing, ocular redness, and itchy ears/palate).
- An important efficacy endpoint that may be analyzed in the studies is the AM NOW total symptom score. This parameter measures the total symptom relief by the patient after 24 hours before taking the next day dose.
- compositions of the present invention may be particularly useful for the treatment and prevention of the nasal (stuffiness/congestion, rhinorrhea, nasal itching, sneezing) and non-nasal (itchy/burning eyes, tearing/watery eyes, redness of the eyes, itching of the ears/palate) symptoms of seasonal and perennial allergic rhinitis, including nasal congestion, in patients in need of such treating and/ or preventing.
- nasal saliva
- rhinorrhea nasal itching, sneezing
- non-nasal itchy/burning eyes, tearing/watery eyes, redness of the eyes, itching of the ears/palate symptoms of seasonal and perennial allergic rhinitis, including nasal congestion, in patients in need of such treating and/ or preventing.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002575932A CA2575932A1 (en) | 2004-08-04 | 2005-08-03 | Pharmaceutical formulations comprising pleconaril for the treatment of airway diseases |
MX2007001561A MX2007001561A (en) | 2004-08-04 | 2005-08-03 | Pharmaceutical formulations comprising pleconaril for the treatment of airway diseases. |
JP2007524916A JP2008509143A (en) | 2004-08-04 | 2005-08-03 | Pharmaceutical formulations containing pleconaril for the treatment of airway diseases |
EP05782421A EP1819329A2 (en) | 2004-08-04 | 2005-08-03 | Pharmaceutical formulations comprising pleconaril for the treatment of airway diseases |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US59861804P | 2004-08-04 | 2004-08-04 | |
US60/598,618 | 2004-08-04 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2006017505A2 true WO2006017505A2 (en) | 2006-02-16 |
WO2006017505A3 WO2006017505A3 (en) | 2006-12-14 |
Family
ID=35583475
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2005/027428 WO2006017505A2 (en) | 2004-08-04 | 2005-08-03 | Pharmaceutical formulations comprising pleconaril for the treatment of airway diseases |
Country Status (6)
Country | Link |
---|---|
US (1) | US20060030550A1 (en) |
EP (1) | EP1819329A2 (en) |
JP (2) | JP2008509143A (en) |
CA (1) | CA2575932A1 (en) |
MX (1) | MX2007001561A (en) |
WO (1) | WO2006017505A2 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007095039A2 (en) * | 2006-02-09 | 2007-08-23 | Schering Corporation | Pharmaceutical formulations |
WO2007095043A2 (en) * | 2006-02-09 | 2007-08-23 | Schering Corporation | Pharmaceutical formulations |
WO2008033155A1 (en) * | 2006-09-15 | 2008-03-20 | Auriga Laboratories, Inc. | Kits for prevention and treatment of rhinitis |
WO2010009288A1 (en) * | 2008-07-17 | 2010-01-21 | Schering Corporation | Compositions and uses of antiviral active pharmaceutical agents |
WO2015070181A1 (en) | 2013-11-08 | 2015-05-14 | Anitvirus Therapeutics | Methods and compositions for treating sepsis |
CN111166719A (en) * | 2019-12-31 | 2020-05-19 | 郑州都灵兽药科技有限公司 | Preparation method of tulathromycin enteric-coated granules |
US11554229B2 (en) | 2013-03-26 | 2023-01-17 | OptiNose Inc. | Nasal administration |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7902177B2 (en) * | 2005-05-02 | 2011-03-08 | Wandzel Richard A | Treatment of congestion using steroids and adrenergics |
EP1981475A2 (en) * | 2006-02-09 | 2008-10-22 | Schering Corporation | Pharmaceutical formulations |
CN1907293B (en) * | 2006-08-22 | 2012-07-04 | 蔡海德 | Combined medicine for treating lpneumonia and preparing process thereof |
WO2009079078A1 (en) | 2007-12-14 | 2009-06-25 | Labogroup S.A.S. | Delivering aerosolizable food products |
US20110092493A1 (en) * | 2008-09-24 | 2011-04-21 | Clark Levi | Dose-controlled transdermal promethazine compositions and methods of use |
US9757395B2 (en) | 2012-12-20 | 2017-09-12 | Otitopic Inc. | Dry powder inhaler and methods of use |
US9757529B2 (en) | 2012-12-20 | 2017-09-12 | Otitopic Inc. | Dry powder inhaler and methods of use |
EP3607941A1 (en) | 2013-04-30 | 2020-02-12 | Otitopic Inc. | Dry powder formulations and methods of use |
EP3160556A1 (en) * | 2014-06-25 | 2017-05-03 | Optinose AS | Nasal administration |
US10139321B2 (en) * | 2016-07-29 | 2018-11-27 | Alpha-Tec Systems, Inc. | Mucolytic tablet for a sample collection device |
CN107669635A (en) * | 2016-09-30 | 2018-02-09 | 青岛大学 | It is a kind of to be used to treat aerosol of respiratory disease and preparation method thereof |
CN107513071B (en) * | 2017-08-30 | 2019-06-04 | 新乡医学院 | A kind of multi-functional podophyllotoxin derivative and its preparation method and application |
US10786456B2 (en) | 2017-09-22 | 2020-09-29 | Otitopic Inc. | Inhaled aspirin and magnesium to treat inflammation |
KR102507987B1 (en) | 2017-09-22 | 2023-03-21 | 벡추라 인코포레이티드 | Dry Powder Composition with Magnesium Stearate |
CN114177176B (en) * | 2021-12-04 | 2022-07-12 | 中国农业科学院兰州兽医研究所 | Application of compound cyproheptadine hydrochloride in preparation of drug for preventing or treating African swine fever |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5643929A (en) * | 1992-04-15 | 1997-07-01 | Sanofi Winthrop, Inc. | 1,2,4-oxidiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents |
WO2002005814A1 (en) * | 2000-07-18 | 2002-01-24 | Smithkline Beecham Corporation | Use of il-8 receptor antagonists in the treatment of virus infections |
WO2002009699A2 (en) * | 2000-07-28 | 2002-02-07 | Immupharm Aps | Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract |
WO2003020271A1 (en) * | 2001-08-29 | 2003-03-13 | Viropharma Incorporated | Oxadiazolyl-phenoxyalkylisoxazoles, compositions thereof and methods for their use as anti-picornaviral agents |
WO2003065988A2 (en) * | 2002-02-04 | 2003-08-14 | Pharmacia Corporation | A combination for treating cold and cough |
WO2003068222A1 (en) * | 2002-02-14 | 2003-08-21 | Viropharma Incorporated | Methods of reducing rhinovirus contagion and related compositions |
WO2004094370A2 (en) * | 2002-09-10 | 2004-11-04 | Microbiotix, Inc. | Antibacterial pyrazole carboxylic acid hydrazides |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1618005A1 (en) * | 1966-09-22 | 1971-09-09 | Thomae Gmbh Dr K | Process for the preparation of new amino-dihalogen-phenyl-ethylamines |
US4282233B1 (en) * | 1980-06-19 | 2000-09-05 | Schering Corp | Antihistaminic 11-(4-piperidylidene)-5h-benzoÄ5,6Ü-cyclohepta-Ä1,2Ü-pyridines |
DE3106995A1 (en) * | 1981-02-25 | 1982-08-19 | Degussa Ag, 6000 Frankfurt | METHOD FOR PRODUCING GUAJOCALGLYCERINETHER |
AU570306B2 (en) * | 1984-02-15 | 1988-03-10 | Schering Corporation | 8-chloro-6, 11-dihydro-11-(4-piperidylidene)-5h-benzo (5,6) cyclohepta (1,2-b) pyridine and its salts. |
US4731447A (en) * | 1985-05-13 | 1988-03-15 | Schering Corporation | Process for preparing piperidylidene dihydro-dibenzo(a,d)-cycloheptenes or aza-derivatives thereof |
DK0656206T3 (en) * | 1991-06-10 | 2001-10-08 | Schering Corp | Aerosol formulations without chlorofluorocarbon compounds |
JP2600644B2 (en) * | 1991-08-16 | 1997-04-16 | 藤沢薬品工業株式会社 | Thiazolyl benzofuran derivative |
US5352707A (en) * | 1992-03-26 | 1994-10-04 | Harbor Branch Oceanographic Institution, Inc. | Method for treating airway congestion |
US5270324A (en) * | 1992-04-10 | 1993-12-14 | Merck Frosst Canada, Inc. | Fluorinated hydroxyalkylquinoline acids as leukotriene antagonists |
US5472964A (en) * | 1992-12-22 | 1995-12-05 | Merck Frosst Canada, Inc. | Diaryl 5,6-fused heterocyclic acids as leukotriene antagonists |
US5837699A (en) * | 1994-01-27 | 1998-11-17 | Schering Corporation | Use of mometasone furoate for treating upper airway passage diseases |
US6068832A (en) * | 1996-08-29 | 2000-05-30 | Schering Corporation | Chlorofluorocarbon-free mometasone furoate aerosol formulations |
US5894179A (en) * | 1997-12-17 | 1999-04-13 | Emerson Electric Co. | Motor with strategically placed connector block |
TR200200673T2 (en) * | 1999-09-17 | 2002-12-23 | Smithkline Beecham Corporation | The use of csaids in rhinovirus infections |
AU3800601A (en) * | 2000-02-03 | 2001-08-14 | Schering Corporation | Treating allergic and inflammatory conditions |
PE20020507A1 (en) * | 2000-10-17 | 2002-06-25 | Schering Corp | NON-IMIDAZOLE COMPOUNDS AS ANTAGONISTS OF THE HISTAMINE H3 RECEPTOR |
AUPR213700A0 (en) * | 2000-12-18 | 2001-01-25 | Biota Scientific Management Pty Ltd | Antiviral agents |
GB0123951D0 (en) * | 2001-10-05 | 2001-11-28 | Glaxo Group Ltd | Therapies for treating respiratory diseases |
CA2495689A1 (en) * | 2002-08-23 | 2004-03-04 | Schering Corporation | Pharmaceutical compositions |
-
2005
- 2005-08-03 MX MX2007001561A patent/MX2007001561A/en unknown
- 2005-08-03 WO PCT/US2005/027428 patent/WO2006017505A2/en active Application Filing
- 2005-08-03 CA CA002575932A patent/CA2575932A1/en not_active Abandoned
- 2005-08-03 US US11/196,745 patent/US20060030550A1/en not_active Abandoned
- 2005-08-03 JP JP2007524916A patent/JP2008509143A/en active Pending
- 2005-08-03 EP EP05782421A patent/EP1819329A2/en not_active Withdrawn
-
2008
- 2008-07-25 JP JP2008192563A patent/JP2008297311A/en active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5643929A (en) * | 1992-04-15 | 1997-07-01 | Sanofi Winthrop, Inc. | 1,2,4-oxidiazolyl-phenoxyalkylisoxazoles and their use as antiviral agents |
WO2002005814A1 (en) * | 2000-07-18 | 2002-01-24 | Smithkline Beecham Corporation | Use of il-8 receptor antagonists in the treatment of virus infections |
WO2002009699A2 (en) * | 2000-07-28 | 2002-02-07 | Immupharm Aps | Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract |
WO2003020271A1 (en) * | 2001-08-29 | 2003-03-13 | Viropharma Incorporated | Oxadiazolyl-phenoxyalkylisoxazoles, compositions thereof and methods for their use as anti-picornaviral agents |
WO2003065988A2 (en) * | 2002-02-04 | 2003-08-14 | Pharmacia Corporation | A combination for treating cold and cough |
WO2003068222A1 (en) * | 2002-02-14 | 2003-08-21 | Viropharma Incorporated | Methods of reducing rhinovirus contagion and related compositions |
WO2004094370A2 (en) * | 2002-09-10 | 2004-11-04 | Microbiotix, Inc. | Antibacterial pyrazole carboxylic acid hydrazides |
Non-Patent Citations (9)
Title |
---|
ANZUETO A ET AL: "Diagnosis and treatment of rhinovirus respiratory infections" CHEST 01 MAY 2003 UNITED STATES, vol. 123, no. 5, 1 May 2003 (2003-05-01), pages 1664-1672, XP002392817 ISSN: 0012-3692 * |
FLOREA N R ET AL: "PLECONARIL, A NOVEL ANTIPICORNAVIRAL AGENT" PHARMACOTHERAPY, BOSTON, US, vol. 23, no. 3, March 2003 (2003-03), pages 339-348, XP009035763 ISSN: 0277-0008 * |
GWALTNEY JR J M: "Viral respiratory infection therapy: Historical perspectives and current trials" AMERICAN JOURNAL OF MEDICINE 22 APR 2002 UNITED STATES, vol. 112, no. 6 SUPPL. 1, 22 April 2002 (2002-04-22), pages 33S-41S, XP002392818 ISSN: 0002-9343 * |
HAYDEN FREDERICK G ET AL: "Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: Results of 2 double-blind, randomized, placebo-controlled trials." CLINICAL INFECTIOUS DISEASES, vol. 36, no. 12, 15 June 2003 (2003-06-15), pages 1523-1532, XP002392816 ISSN: 1058-4838 * |
HAYDEN FREDERICK G ET AL: "Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials." ANTIVIRAL THERAPY. MAR 2002, vol. 7, no. 1, March 2002 (2002-03), pages 53-65, XP002373367 ISSN: 1359-6535 * |
MCMILLAN R M: "Leukotrienes in respiratory disease." PAEDIATRIC RESPIRATORY REVIEWS. SEP 2001, vol. 2, no. 3, September 2001 (2001-09), pages 238-244, XP002392819 ISSN: 1526-0542 * |
MOSSAD S B: "Current and future therapeutic approaches to the common cold" EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 2003 UNITED KINGDOM, vol. 1, no. 4, 2003, pages 619-626, XP009070282 ISSN: 1478-7210 * |
NOLAN M A ET AL: "Survival after pulmonary edema due to enterovirus 71 encephalitis." NEUROLOGY, vol. 60, no. 10, 27 May 2003 (2003-05-27), pages 1651-1656, XP002373366 ISSN: 0028-3878 * |
SCHIFF G M ET AL: "Clinical activity of pleconaril in an experimentally induced coxackievirus A21 respiratory infection" JOURNAL OF INFECTIOUS DISEASES, CHICAGO, IL, US, vol. 181, no. 1, 2000, pages 20-26, XP002964873 ISSN: 0022-1899 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007095039A2 (en) * | 2006-02-09 | 2007-08-23 | Schering Corporation | Pharmaceutical formulations |
WO2007095043A2 (en) * | 2006-02-09 | 2007-08-23 | Schering Corporation | Pharmaceutical formulations |
WO2007095043A3 (en) * | 2006-02-09 | 2007-12-21 | Schering Corp | Pharmaceutical formulations |
WO2007095039A3 (en) * | 2006-02-09 | 2008-05-08 | Schering Corp | Pharmaceutical formulations |
JP2009526062A (en) * | 2006-02-09 | 2009-07-16 | シェーリング コーポレイション | Pharmaceutical formulation |
WO2008033155A1 (en) * | 2006-09-15 | 2008-03-20 | Auriga Laboratories, Inc. | Kits for prevention and treatment of rhinitis |
WO2010009288A1 (en) * | 2008-07-17 | 2010-01-21 | Schering Corporation | Compositions and uses of antiviral active pharmaceutical agents |
US11554229B2 (en) | 2013-03-26 | 2023-01-17 | OptiNose Inc. | Nasal administration |
WO2015070181A1 (en) | 2013-11-08 | 2015-05-14 | Anitvirus Therapeutics | Methods and compositions for treating sepsis |
CN111166719A (en) * | 2019-12-31 | 2020-05-19 | 郑州都灵兽药科技有限公司 | Preparation method of tulathromycin enteric-coated granules |
Also Published As
Publication number | Publication date |
---|---|
WO2006017505A3 (en) | 2006-12-14 |
EP1819329A2 (en) | 2007-08-22 |
JP2008509143A (en) | 2008-03-27 |
JP2008297311A (en) | 2008-12-11 |
US20060030550A1 (en) | 2006-02-09 |
MX2007001561A (en) | 2007-04-16 |
CA2575932A1 (en) | 2006-02-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20060030550A1 (en) | Pharmaceutical formulations | |
JP2008509143A5 (en) | ||
US20090221541A1 (en) | Pharmaceutical formulations | |
US20060110449A1 (en) | Pharmaceutical composition | |
EP2486942B1 (en) | Compositions comprising azelastine and methods of use thereof | |
US20070202050A1 (en) | Pharmaceutical Formulations | |
US8758816B2 (en) | Compositions comprising azelastine and methods of use thereof | |
US20100144610A1 (en) | Pharmaceutical formulations | |
US20070020330A1 (en) | Compositions comprising azelastine and methods of use thereof | |
JP2011528355A (en) | Intranasal crude product containing decongestant and corticosteroid |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2575932 Country of ref document: CA Ref document number: 2007524916 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/a/2007/001561 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005782421 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2005782421 Country of ref document: EP |